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Table 1 Sensitivity of cell lines to gemcitabine alone or in combination with MK-8776

From: Sensitization of human cancer cells to gemcitabine by the Chk1 inhibitor MK-8776: cell cycle perturbation and impact of administration schedule in vitro and in vivo

A. Gemcitabine and MK-8776 0–24 h

Cell line

IC50(nmol/L)

 

Gem alone

Gem + 200 nmol/L MK-8776

Gem + 2 μmol/L MK-8776

U251

36.6 ± 8.8

15 ± 5.5 (2.4)

6.5 ± 1.5 (5.6)

HCT115

25 ± 5

13.8 ± 1.3 (1.8)

5.1 ± 1.1 (4.9)

SW620

83.3 ± 16

30 ± 0 (2.8)

4.8 ± 0.9 (17.4)

IGROV-1

25 ± 5

5.2 ± 1.1 (4.8)

3.5 ±1.5 (7.1)

HCT116

13.8 ± 1.3

5.5 ± 0.5 (2.5)

3.3 ± 0.3 (4.2)

MCF10A

13 ± 6.1

5.2 ± 2.4 (2.5)

2.8 ± 1.1 (4.6)

MiaPaCa-2

26.5 ± 4.3

4.2 ± 0.8 (6.3)

2.2 ± 1.2 (12.0)

MDA-MB-231

18.5 ± 7.1

4.4 ± 0.81 (4.2)

1.5 ± 0.44 (12.3)

HCC2998

15 ± 5

3.8 ± 1.3 (3.9)

1.5 ± 0.4 (10.0)

U87

7.5 ± 1.3

2.7 ± 0.4 (2.8)

1.5 ± 0.3 (5.0)

MDA-MB-435

8.6 ± 3.2

1.5 ± 1.5 (5.7)

0.4 ± 0 (21.5)

SNB19

10 ± 3.5

1.3 ± 0.08 (7.7)

0.15 ± 0.03 (66.7)

U20S

32.5 ± 2.5

10.5 ± 4.5 (3.1)

DEAD

A498

22.5 ± 2.5

3.5 ± 1.5 (6.4)

DEAD

TK10

3.4 ± 1.6

2.8 ± 1.3 (1.2)

DEAD

AsPC-1

14 ± 1

3.3 ± 0.2 (4.2)

DEAD

B. Gemcitabine 0–24 h; MK-8776 18–24 h

U251

36.6 ± 8.8

32.5 ± 2.5 (1.1)

12.5 ± 2.5 (2.9)

MDA-MB-231

18.5 ± 7.1

12.5 ± 5.5 (1.5)

4.6 ± 0.8 (4.0)

U87

7.5 ± 1.3

5 ± 0.6 (1.5)

2.8 ± 0.16 (2.7)

MDA-MB-435

8.6 ± 3.2

8 ± 2 (1.1)

0.77 ± .73 (11.2)

AsPC-1

14 ± 1

7.8 ± 2.2 (1.8)

1.7 ± 0.23 (8.2)

C. Gemcitabine 0–6 h; MK8776 18–24 h

U251

250 ± 51

187 ± 38 (1.3)

113 ± 18.5 (2.2)

MiaPaCa-2

175 ± 25

90 ± 35 (1.9)

39 ± 1 (4.5)

MDA-MB-231

60.5 ± 10.3

35 ± 9.6 (1.7)

19.2 ± 2.3 (3.2)

U87

12.6 ± 3.9

9 ± 2.1 (1.4)

5.3 ± 0.9 (2.4)

MDA-MB-435

41.6 ± 19.7

22.5 ± 7.5 (1.8)

5.5 ± 2.5 (7.6)

SNB19

75 ± 0

35 ± 5 (2.1)

16.5 ± 1.5 (4.5)

AsPC-1

115 ± 11.9

53.3 ± 6.7 (2.2)

12 ± 1.7 (9.6)

  1. Following treatment as indicated, drugs were removed and cells were incubated for an additional 5–7 days and the IC50 for gemcitabine determined.
  2. Values reflect mean +/− SEM with n = 2–5; parenthesis = fold sensitization.
  3. “DEAD” = MK-8776 alone markedly suppressed growth so no cumulative cytotoxicity calculable.